Abstract
Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4+ T cell memory subsets from HIV+ subjects. In the HIV-negative setting, SM treatment showed trends towards suppressing pro-inflammatory cytokines from non-activated and pathogen-associated molecular pattern (PAMP)-activated primary human monocytes, and non-activated and cytokine- and T cell receptor (TCR)-activated mucosal-associated invariant T (MAIT) cells. The data suggest that SM elicits broad anti-inflammatory and immunoregulatory activity in primary human immune cells. By using novel compounds to alter cellular inflammatory status, it may be possible to regulate inflammation in both non-disease and disease states.
Highlights
Inflammation is a protective and reparative response that is induced by pathogen or hostderived engagement of pattern recognition receptors (PRR) as well as through the engagement of cytokine and non-cytokine cellular receptors [1, 2]
The data suggest that SM treatment suppresses inflammation in resting and pathogen-associated molecular pattern (PAMP), cytokine, and T cell receptor (TCR)-activated primary human monocyte and CD8+ mucosal-associated invariant T (MAIT) cell types
We show that SM significantly reduces expression of various markers of T cell activation and exhaustion (e.g., CD38, HLA-DR, cytotoxic T lymphocyte antigen 4 (CTLA4), and PD1) as well as pro-inflammatory cytokines (e.g., IL-6 and IL-18) in peripheral blood mononuclear cell (PBMC) from chronically-infected human immunodeficiency virus (HIV)-positive subjects
Summary
Inflammation is a protective and reparative response that is induced by pathogen or hostderived engagement of pattern recognition receptors (PRR) as well as through the engagement of cytokine and non-cytokine cellular receptors [1, 2]. Receptor activation triggers cellular signal transduction, causing production and release of pro-inflammatory cytokines and chemokines from cells, which in turn, recruits immune effector cells to the site of inflammation. Upon resolution of infection and/or damage, inflammatory responses normally return to PLOS ONE | DOI:10.1371/journal.pone.0171139. Anti-inflammatory effects of silymarin on primary human cells The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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